Cannabinoids from marijuana also appear to be similar to codeine for treatment of pain. However, extreme sleepiness and other central nervous system effects make cannabinoids undesirable as painkillers.

Other cannabinoids from marijuana have also been used by mouth to treat symptoms of multiple sclerosis (MS).

Cyclic Antidepressants

On October 15, 2004, the FDA has concluded that antidepressant medications increase the risk of suicidal thinking and behavior in children and adolescents with depression and other psychiatric disorders. If you have questions or concerns, discuss them with your health care provider

"What I remember most about being depressed was always being exhausted. I could never get to sleep at night, and when I did, I had nightmares. Then I'd wake up in the morning and have to drag myself to work. And in all that time—four or five years, I guess—I never once enjoyed anything. I was actually planning my own suicide when my doctor referred me to a psychiatrist who put me on imipramine. For the first time in years, I finally began to get some pleasure out of life."

—Sam, 43

Before the SSRIs, tricyclics were the first line of defense against encroaching depression, and had been ever since imipramine's release in 1958 under the brand name Tofranil.

Today, tricyclics are a less popular choice than the new generation of antidepressants, but they're still an important weapon in the antidepressant arsenal for a subset of people who don't respond to anything else.

Before tricyclics were developed, psychiatrists treating severely depressed clients had only two real choices: amphetamines or electroshock therapy.

Imipramine was discovered by Swiss scientists searching for a successful schizophrenia treatment; it turned out that imipramine didn't do much for schizophrenia at all. What it did do very well was perk up depressed patients.

Common Cyclic Antidepressants

Lower doses are used with elderly patients)

Drug

Usual Effective Daily Dose

Amitriptyline (Elavil, Endep, Emitrip, Enovil)

150–300 mg

Amoxapine (Asendin)

150–400 mg

Clomipramine (Anafranil)

100–150 mg

Desipramine (Norpramin, Pertofrane)

100–300 mg

Doxepin (Adapin, Sinequan)

75–300 mg

Imipramine (Janimine, Tipramine, Tofranil, Tofranil-PM)

150–300 mg

Maprotiline (Ludiomil)

75–150 mg

Nortriptyline (Pamelor, Aventyl)

50–150 mg

Protriptyline (Vivactil)

15–60 mg

Trimipramine (Surmontil)

75–150 mg

With the discovery of imipramine, doctors finally had a drug that relieved a person's underlying depression.

When scientists realized how effective imipramine was—about 70 percent of depressed patients responded to this drug—they flocked to the laboratories in search of similar drugs based on imipramine's three-ring ("tricyclic") antihistaminic chemical structure.

Before long, laboratories all over the country began churning out tricyclic clones, each one a little different from, but none any better than, imipramine itself.

A later-developed drug in this class, maprotiline (Ludiomil), had four rings and was therefore called "tetracyclic." Taken together, the tricyclics and tetracyclics are known as "heterocyclics" or "cyclics."

But while all these cyclics were effective, not one provided the perfect solution to depression for which scientists had been searching.

Cannabinoids, in combination with (NSAIDS), produce a synergistic analgesic effect

Ankara, Turkey: Cannabinoids, when administered in combination with non-steroidal anti-inflammatory drugs (NSAIDS), produce a synergistic analgesic effect, according to preclinical data published in the February issue of the journal Anesthesia & Analgesia.

A research team at the Trakya University in Turkey investigated the analgesic interaction between cannabinoids and NSAIDS in mice. "Analysis showed additive interactions between [cannabinoids] and [NSAIDS] when they were co-administered systematically in an inflammatory visceral pain model," investigators concluded. "The combination of cannabinoids and NSAIDS may have utility in the pharmacotherapy of pain."

Add-on treatment with the synthetic cannabinomimetic nabilone on patients with chronic pain

Title

[Benefits of an add-on treatment with the synthetic cannabinomimetic nabilone on patients with chronic pain - a randomized controlled trial.] [Article in German]

Author(s)

Pinsger M, Schimetta W, Volc D, Hiermann E, Riederer F, Polz W.

Journal, Volume, Issue

Wien Klin Wochenschr. 2006 Jun;118(11-12):327-35.

Major outcome(s)

Nabilone caused a significant reduction in pain and improvement of quality of life.

Indication

Pain

Abstract

Medication

Nabilone

OBJECTIVE: The aim of this study was to investigate the efficacy and efficiency of an add-on treatment with the synthetic cannabinomimetic nabilone on patients with chronic pain.

Of major interest were the evaluation of the influence the treatment had on pain and on quality of life as well as the subjective assessment of positive effects and side effects by the study participants.

METHODS: The placebo-controlled double-blinded pilot study was divided into a 14 week cross-over period (two 4 week medication phases plus wash-out phases) followed by a 16 week medication switch period with free choice of the study drugs (drug A and drug B) by the study participants.

The principal inclusion criterion was chronic therapy-resistant pain in causal relationship with a pathologic status of the skeletal and locomotor system.

The study participants chose the dosage of the study drug themselves (between 1 und 4 capsules/day, in the case of nabilone this corresponds to (1/4)-1 mg/day).

Pain intensity was assessed by a visual analogue scale (VAS), quality of life by the Mezzich & Cohen QOL-score. RESULTS: Altogether, 30 patients were included and analyzed.

From the results, it is obvious that throughout the cross-over periods the nabilone treatment was superior (medians [25%-; 75%-percentiles]: nabilone/placebo): decrease of the average spinal pain intensity within the last 4 weeks (DeltaVAS) 0.9 [0.0; 2.0] / 0.5 [0.0; 1.7], decrease of the current spinal pain intensity (DeltaVAS) 0.6 [0.0; 2.5] / 0.0 [-1.0, 1.0] (p = .006), decrease of the average headache intensity within the last 4 weeks (DeltaVAS) 1.0 [-1.0; 2.4] / 0.2 [-0.9; 1.0], increase of the number of days without headache within the last 4 weeks 2.0 [0.0; 6.5] / 0.0 [-5.0; 4.0], increase of the quality of life (DeltaQOL-Score) 5.0 [0.8; 10.8] / 2.0 [-2.3; 8.0].

In the medication switch period, the number of study participants who favoured nabilone (nabilone intake >/=85% of all medication days) was more than 4 times higher than those who favoured placebo.

The number of days with nabilone intake was clearly higher than the number with placebo intake (medians: 89% vs. 11% of all medication days, p = .003).

CONCLUSION: In summary, the study results allow the conclusion that a majority of patients with chronic pain classify nabilone intake in addition to the standard treatment as a measure with a positive individual benefit-riskratio.

Thus, this kind of treatment may be an interesting and attractive enrichment of analgetic therapy concepts.

Fifteen minutes later subjects rated the pain associated with the application of thermal stimuli to skin using two visual analog scales, one for the sensory and one for the affective aspects of pain.

Among sensory responses, neither morphine nor Delta(9)-THC had a significant effect at the doses used, and there was no significant interaction between the two.

Among affective responses, although neither morphine nor Delta(9)-THC had a significant effect, there was a positive analgesic interaction between the two (p=0.012), indicating that the combination had a synergistic affective analgesic effect.

The surprisingly limited reported experimental experience in humans does not support a role for Delta(9)-THC as an analgesic or as an adjunct to cannabinoid analgesia, except for our finding of synergy limited to the affective component of pain.

Comparison of our results with those of others suggests that extrapolation from experimental pain models to the clinic is not likely to be a straight-forward process.

Future studies of Delta(9)-THC or other cannabinoids in combination with opiates should focus upon clinical rather than experimental pain.

Synergy between Delta(9)-tetrahydrocannabinol and morphine in the arthritic rat

We have shown in past isobolographic studies that a small amount of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) can enhance morphine antinociception in mice. However, previous studies of the Delta(9)-THC/morphine interaction were performed using normal mice or rats and evaluated acute thermal antinociception.

Less is known about cannabinoid and opioid interactions involved in mechanical nociception and in chronic inflammatory pain models, such as Freund's complete adjuvant-induced arthritic model. One fixed-ratio combination was chosen for testing the interaction between Delta(9)-THC and morphine in the Freund's adjuvant-induced arthritic model.

This combination represented a 1:1 ratio of the drugs and thus consisted of equieffective doses ranging from 0.1 to 5 mg/kg Delta(9)-THC and from 0.1 to 5 mg/kg morphine. The combination ED(50) value for the fixed ratios (total dose) in relation to the ED(50) value of the drugs alone was determined.

The isobolographic analysis indicated a synergistic interaction between Delta(9)-THC and morphine in both the non-arthritic and the arthritic rats.

Since Freund's adjuvant-induced alteration in endogenous opioid tone has been previously shown, our data indicate that such changes did not preclude the use of Delta(9)-THC and morphine in combination. As with acute preclinical pain models in which the Delta(9)-THC/morphine combination results in less tolerance development, the implication of the study for chronic pain conditions is discussed.

No abstract available. First of three case reports: A 47-year-old woman with a ten-year history of chronic progressive multiple sclerosis (MS) head headache, multisite joint pain, bladder spasm, and leg spasticity.

Ambulation was significantly compromised by the joint pain and leg spasticity.

She was wheelchair dependent, and also suffered from severe insomnia and fatigue, which she attributed to the combination of pain, bladder spasm, and leg spasticity.

Recently, a standardized medicinal cannabis product was introduced in The Netherlands.

We anticipated an increased use of medicinal cannabis concurrent with anticancer drugs, and undertook a drug-INTERACTION study to evaluate the effect of concomitant medicinal cannabis on the pharmacokinetics of irinotecan and docetaxel, both subject to CYP3A-mediated biotransformation.

Blood samples were obtained up to 55 hours after dosing and analyzed for irinotecan and its metabolites (SN-38, SN-38G), respectively, or docetaxel.

Pharmacokinetic analyses were performed during both treatments. Results are reported as the mean ratio (95% confidence interval [CI]) of the observed pharmacokinetic parameters with and without concomitant medicinal cannabis.

Interaction of cannabis and general anaesthetic agents in mice

1 A cannabis extract (I) (in a concentration equivalent to 10 mg Δ9-tetrahydro-cannabinol(THC)/kg) prolonged pentobarbitone anaesthesia in mice maximally 20 min to 2 h after medication. The effect was still significant after 8 h, but less than at 2 hours.

2 The cannabis extract (I) (equivalent to 10 mg Δ9-THC/kg) prolonged both pentobarbitone and ether anaesthesia in mice when administered 20 min before the anaesthetic. After eight consecutive daily doses of cannabis, the pentobarbitone anaesthesia was still significantly longer than a control group, while ether anaesthesia was not significantly prolonged.

3 A second cannabis extract (II) with a different ratio of cannabinoids (also administered in dosage equivalent to 10 mg Δ9-THC/kg) failed to affect pentobarbitone anaesthesia in mice. This extract presented about 4% the dose of cannabidiol as extract I.

7 It is concluded that cannabis may affect pentobarbitone and ether anaesthesia in mice at least partially by a direct depressant effect, and that the cannabis-induced prolongation of anaesthesia is probably unrelated to any effect on central 5-hydroxytryptamine or catecholamine neurones.

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (883K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Cannabis Coadministration Potentiates the Effects of "Ecstasy" on Heart Rate and Temperature in Humans

This study assessed the acute physiologic effects over time of (co)administration of Delta9-tetrahydrocannabinol (Delta9-THC) (the main psychoactive compound of cannabis) and 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") in 16 healthy volunteers.

Pharmacokinetics and cardiovascular, temperature, and catecholamine responses were assessed over time.

These effects may be of particular relevance for the cardiovascular safety of ecstasy users who participate in energetic dancing in nightclubs with high ambient temperature.Clinical Pharmacology & Therapeutics (2009); advance online publication 13 May 2009. doi:10.1038/clpt.2009.62.

Enhancing the in vitro cytotoxic activity of Δ9-tetrahydrocannabinol in leukemic cells through a combinatorial approach

Author(s)

Abstract

Δ9-Tetrahydrocannabinol (THC) is the active metabolite of cannabis, which has demonstrable cytotoxic activity in vitro. In support of our previously published data, we have investigated the interactions between THC and anti-leukemia therapies and studied the role of the signalling pathways in mediating these effects.

Additionally, exposure of cells to sub lethal levels of THC (1 μM) sensitised cells to these cytotoxic agents, by reducing IC50 values by ∼ 50%. Sensitisation appeared to be dependent upon the ability of THC to down regulate phosphorylated ERK, as cells dominantly expressive of MEK were not sensitised to the cytotoxic drugs by equi-molar amounts of THC.

Overall, these results demonstrate for the first time that a combination approach with THC and established cytotoxic agents may enhance cell death in vitro. Additionally the MAPK/ERK pathway appears responsible in part for these effects.

The multidrug transporter ABCG2 (BCRP) is inhibited by plant-derived cannabinoids

Source

Abstract

BACKGROUND AND PURPOSE:

Cannabinoids are used therapeutically for the palliation of the adverse side effects associated with cancer chemotherapy. However, cannabinoids also inhibit both the activity and expression of the multidrug transporter, P-glycoprotein in vitro.

Here we address the interaction of cannabinol (CBN), cannabidiol (CBD) and delta 9-tetrahydrocannabinol (THC) with the related multidrug transporter, ABCG2.

EXPERIMENTAL APPROACH:

The cytotoxicity and chemosensitization by cannabinoids was determined with cell viability assays. Expression of cannabinoid and vanilloid receptors was assessed using reverse transcriptase polymerase chain reaction, and cannabinoid modulation of ABCG2 expression was examined using immunoblotting.

KEY RESULTS:

CBN, CBD and THC increased the intracellular accumulation of the Abcg2/ABCG2 substrate, mitoxantrone, in an over-expressing cell line.

The THC metabolite, (-)-11-nor-9-carboxy-delta 9-THC was much less potent.

The plant cannabinoids inhibited both basal and substrate stimulated ATPase activity of human ABCG2. Cannabinoid cytotoxicity occurred in the absence of known cannabinoid cell surface receptors, and only at concentrations higher than those required for Abcg2/ABCG2 inhibition.

Sub-toxic concentrations of the cannabinoids resensitized the overexpressing cell line to the cytotoxic effect of Abcg2/ABCG2 substrates, mitoxantrone and topotecan. This occurred in the absence of any effect on ABCG2 expression.

CONCLUSIONS AND IMPLICATIONS:

Cannabinoids are novel Abcg2/ABCG2 inhibitors, reversing the Abcg2-mediated multidrug-resistant phenotype in vitro. This finding may have implications for the co-administration of cannabinoids with pharmaceuticals that are ABCG2 substrates.

Dronabinol was as effective as ondansetron in reducing nausea and vomiting. Combination therapy was not more effective.

Indication

Nausea/vomiting;Cancer;Cancer chemotherapy

Abstract

Medication

Delta-9-THC

OBJECTIVE: To compare the efficacy and tolerability of dronabinol, ondansetron, or the combination for delayed chemotherapy-induced nausea and vomiting (CINV) in a 5-day, double-blind, placebo-controlled study.

RESEARCH DESIGN AND METHODS: Patients receiving moderately to highly emetogenic chemotherapy received dexamethasone (20 mg PO), ondansetron (16 mg IV) and either placebo or dronabinol (2.5 mg) prechemotherapy on day 1. Patients randomized to active treatment (dronabinol and/or ondansetron) also received dronabinol (2.5 mg) after chemotherapy on day 1.

Induction dose of propofol in patients using cannabis

BACKGROUND AND OBJECTIVE: An estimated 150 million people worldwide use cannabis.

The effect of cannabis on anaesthetic requirements in humans does not appear to have been studied.

METHODS: In this prospective, randomized, single-blinded study, 30 male patients using cannabis more than once per week (group C) and 30 nonusers (group NC), aged 18-50 years, were induced with propofol 1.5, 2, 2.5, 3 or 3.5 mg kg.

Additional doses were given when required. The primary outcome was the 50% effective dose of propofol and successful induction was determined by loss of consciousness with a bispectral index value of less than 60 and satisfactory insertion of a laryngeal mask. Propofol requirements to achieve these outcomes were recorded.

Smoking Pot, Cigarettes Ups COPD Risk

April 13, 2009 -- People who smoke both cigarettes and marijuana have a greater risk for developing the progressive lung disease COPD than cigarette smokers who don't smoke pot, a new study shows.

Smokers in the study who reported using both tobacco and marijuana were three times as likely as nonsmokers to have clinically confirmed COPD (chronic obstructive pulmonary disease); people who smoked only cigarettes had a slightly lower risk.

The study is among the first to suggest a synergistic relationship between marijuana and tobacco use among older people who are most at risk for COPD.

"This effect suggests that smoking marijuana may act as a primer, or sensitizer, in the airways to amplify the adverse effects of tobacco on respiratory health," says study researcher Wan C. Tan, MD, of the University of British Columbia and St. Paul's Hospital in Vancouver, Canada.

COPD Risk

About 12 million Americans are currently living with a diagnosis of COPD; an equal number are believed to have the disease and not know it, according to the National Heart, Lung and Blood Institute.

In the U.S, the term COPD includes both emphysema and chronic bronchitis. With COPD, breathing becomes more difficult over time.

Largely caused by cigarette smoking, COPD is the fourth leading cause of death in the U.S.

While the link between tobacco and COPD is well established, far less is known about the impact of marijuana use on the lungs.

Some studies have found that even short-term heavy marijuana smoking can worsen lung function, while others have not shown this association.

Even less is known about the combined effects of smoking cigarettes and pot, Tan tells WebMD.

The study by Tan and colleagues included 878 residents of Vancouver, Canada participating in a larger investigation examining COPD prevalence.

Participants were considered tobacco smokers if they had smoked at least 365 cigarettes in their lifetime, and were considered marijuana smokers if they reported having ever smoked pot. The researchers defined "substantial" marijuana use as having smoked at least 50 marijuana cigarettes.

The average cigarette smoker in the study had smoked for 16 years, while the self-described pot smokers had smoked an average of 84 marijuana cigarettes.

When COPD was clinically confirmed though a diagnostic method known as spirometric testing:

The incidence of COPD among participants who smoked cigarettes alone was 2.7 times higher than among nonsmokers.

The incidence of COPD was 2.9 times higher among participants with a history of smoking both cigarettes and pot, even after controlling for other risk factors for the pulmonary disease.

COPD risk among people who smoked marijuana, but not tobacco, was slightly higher than among nonsmokers, but the increase was not statistically significant.

The study appears in the April 14 issue of the Canadian Medical Association Journal.

Probable Interaction Between Warfarin and Marijuana Smoking

OBJECTIVE: To report a probable interaction between warfarin and marijuana smoking, resulting in increased international normalized ratio (INR) values and bleeding complications.

CASE SUMMARY: A 56-year-old white male had been receiving chronic warfarin therapy for 11 years after mechanical heart valve replacement. He was admitted to the hospital with a diagnosis of upper gastrointestinal bleeding. Upon admission, his INR value was supratherapeutic at 10.41, and his hemoglobin level was 6.6 g/dL.

He received 4 units of fresh frozen plasma and one 10-mg dose of oral vitamin K; his INR was 1.8 the next day. He was discharged 7 days after admission. Fifteen days after hospital discharge, he was readmitted with a constant nosebleed and increased bruising.

His INR value was 11.55. After treatment, he was discharged with an INR value of 1.14. The patient smoked marijuana more frequently throughout the period of these 2 hospitalizations due to his depression.

He was counseled by the pharmacist on the potential interaction of warfarin and marijuana. The patient decided to stop smoking marijuana after the third counseling session. During the 9 months that he did not smoke marijuana, his INR values ranged from 1.08 to 4.40 with no significant bleeding complications.

DISCUSSION: Marijuana may increase warfarin anticoagulant effect by inhibiting its metabolism, and to a lesser extent, displacing warfarin from protein-binding sites. Other causes (eg, nonadherence) of the patient's increased INR were ruled out. Using the Horn Drug Interaction Probability Scale, our patient's warfarin- marijuana interaction appeared to be probable.

CONCLUSIONS: To our knowledge, there have been no other reported cases of warfarin-marijuana interaction.

While more clinical reports would be useful to confirm this interaction, clinicians should be aware of its probability so as to manage patients appropriately.

Source

Abstract

3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") is an amphetamine derivative with psychostimulant properties.

This substance is widely used around the world by young adults in recreational settings. One of the most remarkable characteristic of ecstasy users is the concurrent consumption of several other drugs of abuse including psychostimulants, alcohol, tobacco, LSD, cannabis and opioids.

This poly-drug pattern of use is now prompting research towards understanding how the combination of MDMA with cannabis and opioids could affect neuropsychobiological processes related to addiction.

As with other drugs of abuse, behavioural evidence has been presented supporting the role of the endocannabinoid system as a modulator of the rewarding/reinforcing properties of MDMA.

On the other hand, the neurochemical substrate for the complex interactions between the endocannabinoid system and MDMA is poorly understood. MDMA also modulates the activity of the dynorphinergic and enkephalinergic systems in several brain structures related to addiction, as it has been shown for other psychostimulants.

The work regarding the contribution of micro- and delta-opioid receptors in the rewarding effects of MDMA shows differential results in pharmacological studies in rats, with respect to studies using knock-out mice. The present review describes the behavioural and neurochemical interactions between MDMA, cannabinoids and opioids with respect to addiction processes.

Source

Abstract

This study assessed the acute physiologic effects over time of (co)administration of Delta9-tetrahydrocannabinol (Delta9-THC) (the main psychoactive compound of cannabis) and 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") in 16 healthy volunteers.

Source

Abstract

Cannabinoids such as Δ-9-tetrahydrocannabinol (THC) release endogenous opioids and endocannabinoids such as anandamide (AEA) also alter endogenous opioid tone.

Opioids and cannabinoids bind distinct receptors that co-localize in areas of the brain involved with the processing of pain signals. Therefore, it is logical to look at interactions of these two systems in the modulation of both acute and chronic pain.

These drugs are often co-abused. In addition, the lack of continued effectiveness of opioids due to tolerance development limits the use of such drugs.

The cost to society and patients in terms of dollars, loss of productivity, as well as quality of life, is staggering.

This review summarizes the data indicating that with cannabinoid/opioid therapy one may be able to produce long-term antinociceptive effects at doses devoid of substantial side effects, while preventing the neuronal biochemical changes that accompany tolerance.

The clinical utility of modulators of the endocannabinoid system as a potential mimic for THC-like drugs in analgesia and tolerance-sparing effects of opioids is a critical future direction also addressed in the review.

Effect of cannabis and certain of its constituents on pentobarbitone sleeping time and phenazone metabolism

1. Cannabis extract prolonged sleeping time in mice in a thermally neutral environment (30-32° C) in which hypothermia does not occur. The prolongation was dose related, just detectable at 50 mg/kg, and 4-fold at 500 mg/kg.

4. Δ1-Tetrahydrocannabinol (Δ1-THC) prolonged pentobarbitone sleep and inhibited phenazone metabolism, but its action was limited, and could not account for the effect of the extract. The carotenes and water-soluble fractions of the extract were inactive on pentobarbitone sleep.

5. Cannabidiol was strongly active by both tests; in vivo 39·8 μM/kg (12·5 mg/kg) prolonged sleep by 190%, and in vitro 12·7 μM inhibited phenazone metabolism 20%. These actions were dose related, and could account for the effect of the extract.

6. The prolongation of pentobarbitone sleep by cannabis extract in a dose of 200 mg/kg, intraperitoneally, was maximal when given 30 min before the pentobarbitone, still present at 3 h, but undetectable at 24 hours. No phase of enhanced metabolism at 24 or 48 h after single cannabis injection was detected.

7. It is concluded that cannabis extract inhibits microsomal activity of mouse liver, chiefly by virtue of its cannabidiol content. It is probable that cannabis consumption by man could lead to altered disposal of many other drugs, used in medicine or otherwise.

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.3M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Early exposure to cannabis, particularly in combination with genetic factors, increases the risk of a subsequent, primary, psychotic disorder.

Because paranoia is a common feature of stimulant abuse and cocaine-dependent individuals frequently endorse a history of cannabis abuse, we examined whether early cannabis exposure, in conjunction with polymorphic variation in the catechol-O-methyl transferase gene (COMT Val158Met), influences the risk for cocaine-induced paranoia (CIP).

METHODS: Cannabis-use history was obtained in 1140 cocaine-dependent individuals from a family-based (affected sibling pair) study using the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA).

Logistic regression and generalized estimating equations' analyses were used to examine the role of adolescent-onset cannabis use (< or =15 years of age) on CIP risk, both controlling for previously implicated CIP risk factors and familial relationships, and considering potential interactions with COMT Val158Met genotype.

RESULTS: Cocaine-dependent individuals who endorsed CIP had significantly higher rates of adolescent-onset cannabis use than those without CIP (62.2% vs. 50.2%; chi(2)=15.2, df=1, p<0.0001), a finding that remained after controlling for sibling correlations and other risk factors.

There were no effects of COMT genotype or genotype by early cannabis onset interactions. A modest (OR=1.4) and nearly significant (p=0.053) effect of CIP status in probands on CIP status in siblings was also noted.

CONCLUSIONS: Adolescent-onset cannabis use increases the risk of CIP in cocaine-dependent individuals. COMT genotype and its interaction with early cannabis exposure did not emerge as significant predictors of CIP. In addition, trait vulnerability to CIP may also be familial in nature.

Induction dose of propofol in patients using cannabis

An estimated 150 million people worldwide use cannabis. The effect of cannabis on anaesthetic requirements in humans does not appear to have been studied.

METHODS:

In this prospective, randomized, single-blinded study, 30 male patients using cannabis more than once per week (group C) and 30 nonusers (group NC), aged 18-50 years, were induced with propofol 1.5, 2, 2.5, 3 or 3.5 mg kg.

Additional doses were given when required. The primary outcome was the 50% effective dose of propofol and successful induction was determined by loss of consciousness with a bispectral index value of less than 60 and satisfactory insertion of a laryngeal mask.